The aim of the proposed research is to provide a determination of the structure of duplex DNA, independent of the X-ray diffraction work that has been done up until now. Methods developed recently for electron microscopy will be applied to the thin, plate-like crystals that are formed by DNA upon gradual precipitation in ethanol. The platelet form of these crystals makes them ideally suited for study by electron microscopy. Electron diffraction patterns and images will be obtained from single crystals, at an electron dose low enough to avoid serious effects of radiation damage. The combination of low-dose image and diffraction data from cyrstals in a given orientation allows a reconstruction of a projection of the specimen structure, while the three dimensional structure can be obtained by using specimens that have been tilted at various angles. Light microscope examination of the crystals formed under different conditions gives the clear impression that crystals formed from DNA strands of a given length may vary in thickness, implying that a certain amount of chain folding occurs in the thinnest crystals, similar to that observed in crystals of other helical polymers. Conditions allowing or enhancing this folding will be investigated, possibly providing some information about the folding of DNA into the compact forms found in vivo. Many of the crystals, particularly those formed with longer strands, have an internal structure. Apparently the mode of crystallization may be affected by conformational changes of the DNA during crystal formation. We will investigate this effect, which may provide crystals containing DNA in different conformations. Structural studies will generally be carried out on crystals containing synthetic DNA of uniform length and base composition, and appropriately thin crystals will be formed by the use of short DNA segments or by the use of conditions that enhance the folding of the strands.